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<div class="pagetitle">Viral Host Protein Interactions</div>

<div class="text">
    The goal of this project is to identify the compendium of host proteins that interact directly with influenza
    viral proteins. The influenza virus is remarkably elegant in that it contains only eight genetic segments
    that code for eleven proteins. This limited set of proteins comprises the entire "toolbox" used by the virus
    to infect the host and co-opt cellular function. Identifying direct host-virus protein interactions will give
    critical insight into molecular mechanisms of infection and possibly lead to the identification of novel
    targets for therapeutic intervention.
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<div class="text">
    We are also using this approach to decipher the molecular basis of known genetic determinants of influenza
    virulence. By comparing the interacting host partners of two versions a single viral protein that are known
    to confer differing pathogenicity, we will determine the specific elements of cellular function that are most
    critical to host response and control of infection.
</div>
<div class="text">
    Initial studies have focused on identification and characterization of host proteins that interact with the viral
    protein, NS1. NS1 is the immuno-modulator of influenza, and pathogenicity of a given influenza strain in
    humans often maps genetically to this protein. Using mass spectrometry-based proteomic approaches along
    with an affinity-tagged replication-competent NS1, we have identified the NS1-host interactions common
    to NS variants from diverse strains, have validated many of these interactions and begun characterizing a
    few of these with respect to their role in the viral lifecycle. We are now interrogating those interactions that
    differentially co-purify with NS1 from highly pathogenic variants in order to define the molecular basis of
    NS1-driven pathogenicity.
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<div class="text">
    In addition, we have extended our proteomic analysis to the polymerase complex and the only other non-
    structural viral protein, NEP. Using similar biochemical strategies to those that have proven successful
    for identifying NS1-host interactions, we have affinity-tagged viral protein PB2 and NEP in a replication-
    competent context. Affinity purification will enable the identification of host proteins that bind directly
    to PB2 as well as to the tripartite polymerase complex that are likely coopted for virus multiplication.
    NEP has been reported to regulate export of vRNPs and may regulate the switch from transcription to
    replication.
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<div class="text">
    Finally, using a highly specific native antibody, we have begun work to identify host proteins that interact
    with the major structural viral protein M1. M1 has been reported to be sufficient for the production of
    virus-like particles and the identification of the M1 interactome should reveal the host proteins necessary
    for viral assembly and budding.
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<div class="text"><b>NS1 Interactome</b></div>
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<div class="text"><b>M1 Interactome</b></div>
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